Back to resultsT-cell Depleted Donor Lymphocyte Infusion (DLI)for Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)
Primary Purpose
Acute Myeloid Leukemia, Myelodysplastic Syndromes
Status
Unknown status
Phase
Phase 1
Locations
Singapore
Study Type
Interventional
Intervention
CD8+ T-cell depleted donor lymphocyte infusion
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring High risk Myelodysplastic Syndrome (MDS)
Eligibility Criteria
Inclusion Criteria: Confirmed diagnosis of AML or high risk MDS in the following disease stages: Induction failure, first or subsequent remission, or untreated first relapse. Patient must have an HLA-compatible donor willing and capable of donating peripheral blood stem cells preferably or bone marrow progenitor cells using conventional techniques, and lymphocytes if indicated (HLA-compatible defined as 5/6 or 6/6 matched related or 6/6 molecular matched unrelated donor) Both patient and donor must sign written informed consent forms. Patients must have: ECOG PS </= 2; Ejective fraction > 40%; DLCO > 40% of predicted; Serum bilirubin </= 1.5x institutional upper limit of normal; SGPT (ALT) and SGOT (AST) </= 2.5x institutional upper limit of normal; Serum creatinine </= 2x upper limit of normal; Creatinine clearance >/= 60mL/min. However, renal dysfunction is not an absolute contraindication for NMT as dialysis can be performed during NMT. Exclusion Criteria: Not fulfilling any of the inclusion criteria Active life-threatening infection Overt untreated infection HIV positivity, hepatitis B or C antigen positivity with active hepatitis Pregnant or lactating women Donor contraindication (HIV seropositive confirmed by Western blot; hepatitis B antigenemia) Unable to donate bone marrow or peripheral blood due to concurrent medical condition
Sites / Locations
- Department of Hematology-Oncology, National University HospitalRecruiting
Outcomes
Primary Outcome Measures
Incidence rate of acute and chronic GVHD
Disease remission rate post CD8+ depleted T-cell DLI
Secondary Outcome Measures
Hematopoietic chimerism and immunologic recovery post CD8+ depleted T-cell DLI
Full Information
NCT ID
NCT00242515
First Posted
October 19, 2005
Last Updated
January 7, 2014
Sponsor
National University Hospital, Singapore
Collaborators
Singapore General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT00242515
Brief Title
T-cell Depleted Donor Lymphocyte Infusion (DLI)for Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)
Official Title
Preemptive CD8+ T-cell Depleted Donor Lymphocyte Infusion (DLI) Following Nonmyeloablative Stem Cell Transplantation (NMT) for Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2014
Overall Recruitment Status
Unknown status
Study Start Date
March 2005 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 2008 (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National University Hospital, Singapore
Collaborators
Singapore General Hospital
4. Oversight
5. Study Description
Brief Summary
Primary Objectives:
This a pilot project to determine the feasibility of the preemptive CD8+ depleted T-cell donor lymphocyte infusion (DLI) in:
Reducing the incidence of graft versus host disease (GVHD) based on standard classification of acute and chronic GVHD
Improving hte disease remission rate in comparison with our previous study results.
Secondary Objectives:
To investigate the impact of CD8+ depleted T-cell DLI in hematopoietic chimerism, and immunologic recovery of transplant patients.
Detailed Description
The scientific investigation in this study protocol:
Define the role of preemptive and specific DLI in preserving the GVL effect in the setting of NMT. The ability of selecting components of T cells for transplant and DLI will allow us to test the hypothesis of distinctive roles in subsets of T cells. It was found that CD8-depleted DLI was administered to prevent relapse after TCD (T-cell depleted) BMT (bone marrow as the stem cell source) or CD34-selected PBSC.
Whether preemptive CD8-depleted DLI can perform this function after nonmyeloablative transplantation (NMT) needs to be established, as proposed in our study. If there turns out to be a role for DLI in these circumstances, a CD8-depleted lymphocyte product that can limit GVHD would be a very attractive option. We would also define the relationship of the level of donor chimerism and disease control.
Investigate the impact of CD8-depleted DLI in NMT at specific doses and time points for the reduction of GVHD. The GVHD pattern may vary between different ethnic populations as suggested by our earlier NMT study. Our current proposed study will further shed light on the optimal GVHD prophylaxis regimen in the Singapore patient population.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndromes
Keywords
High risk Myelodysplastic Syndrome (MDS)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Procedure
Intervention Name(s)
CD8+ T-cell depleted donor lymphocyte infusion
Primary Outcome Measure Information:
Title
Incidence rate of acute and chronic GVHD
Title
Disease remission rate post CD8+ depleted T-cell DLI
Secondary Outcome Measure Information:
Title
Hematopoietic chimerism and immunologic recovery post CD8+ depleted T-cell DLI
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Confirmed diagnosis of AML or high risk MDS in the following disease stages: Induction failure, first or subsequent remission, or untreated first relapse.
Patient must have an HLA-compatible donor willing and capable of donating peripheral blood stem cells preferably or bone marrow progenitor cells using conventional techniques, and lymphocytes if indicated (HLA-compatible defined as 5/6 or 6/6 matched related or 6/6 molecular matched unrelated donor)
Both patient and donor must sign written informed consent forms.
Patients must have:
ECOG PS </= 2;
Ejective fraction > 40%;
DLCO > 40% of predicted;
Serum bilirubin </= 1.5x institutional upper limit of normal;
SGPT (ALT) and SGOT (AST) </= 2.5x institutional upper limit of normal;
Serum creatinine </= 2x upper limit of normal;
Creatinine clearance >/= 60mL/min. However, renal dysfunction is not an absolute contraindication for NMT as dialysis can be performed during NMT.
Exclusion Criteria:
Not fulfilling any of the inclusion criteria
Active life-threatening infection
Overt untreated infection
HIV positivity, hepatitis B or C antigen positivity with active hepatitis
Pregnant or lactating women
Donor contraindication (HIV seropositive confirmed by Western blot; hepatitis B antigenemia)
Unable to donate bone marrow or peripheral blood due to concurrent medical condition
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chien-Shing Chen, MD
Phone
67724613
Email
mdcccs@nus.edu.sg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chien-Shing Chen, MD
Organizational Affiliation
National University Hospital/National University Singapore
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Hematology-Oncology, National University Hospital
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
Individual Site Status
Recruiting
12. IPD Sharing Statement
Learn more about this trial
T-cell Depleted Donor Lymphocyte Infusion (DLI)for Acute Myeloid Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)
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